Antigenic stimulation of the immune system induces a series of reactions which can be mediated by immunological components such as the humoral, cellular or cytokine responses. The directionality of these reactions can be considered to be of a reactive or suppressive nature. For instance, in the context of the present invention, an immune reaction is defined as a response that specifically neutralizes, reduces or eliminates the presence of a specific antigen or set of antigens in a subject. In the context of the present invention, immune suppression is defined as a response that specifically diminishes or reduces an immune reaction or has the capability of blocking an immune reaction from being initiated. Examples of humeral responses that may contribute to an immune reaction can comprise or not be limited to the production of antibodies or proteins involved in complement fixation. Examples of cellular responses that may contribute to an immune reaction can comprise but not be limited to expansion of helper T cells, Natural killer (NK) cells, cytopathic T-lymphocytes (CTLs) and B lymphocytes. Examples of cytokine responses that may contribute to an immune reaction can comprise but not be limited to induction of IFN y and IL-2. Examples of humoral responses that may contribute to an immune suppression reaction can comprise or not be limited to the production of anti-idiotypic antibodies. Examples of cellular responses that may contribute to an immune suppression reaction can comprise but not be limited to expansion of supressor T-cells. Examples of cytokine responses that may contribute to an immune suppression reaction can comprise but not be limited to induction of TGF β, IL-4 and IL-10
The stimulation or manipulation of the immune system can be achieved by the introduction of an antigen or antigens that are foreign to the subject. This reaction is a major source of the body's resistance to colonialization by viral, bacterial or parasitic organisms. The absence of this defense in immuno-compromised individuals has allowed what are called opportunistic infections i.e. infections by organisms that are normally non-pathogenic. Examples of such individuals are patients undergoing chemotherapy or transplantation, AIDS patients and individuals with severe combined immune deficiency. Reactivity to foreign antigen sources is also the source of allergy immune reactions, i.e. immunostimulation caused by exposure to antigenic substances present in the environment including dust, pollen, hair and other materials.
Immune stimulation can also be induced by substances that are native to the subject or are immunologically related to native antigens. An illustrative example of this are antigens that provoke autoimmune responses. Since reactivity to the cells, tissues and organs that make up an organism would be self-destructive, there is a system of control over the induction of this form of immune reactions. The mechanism that is most widely regarded as responsible for this self-limitation has been called clonal deletion. In this model, cells that are stimulated by self-antigens are selectively eliminated in a process that begins shortly after birth. After a certain amount of time, the repertoire of immunogenic responses that remains is devoid of cells capable of responding to these native stimuli. Since clonal deletion is an irreversible process, the existence of auto-immunity has been ascribed to a limited number of cells that were unable to achieve a “threshold” level of stimulation by native antigens. Then at some later point in life when clonal elimination processes were absent, an event or events have occurred that induced a heightened immune response to native antigens.
Other example of an immune response to a native antigen is recognition of tumor antigens. The “immune surveillance” theory proposes that during the course of a lifetime, potentially tumorogenic cells are constantly arising, but they are recognized and purged by immune processes. Although proteins expressed by these cells are derived from the genetic information of the subject, recognition as antigens may still take place when they are mutated or inappropriately expressed in a subject. Growth of a tumor may then take place when there is somehow a breakdown in this surveillance process.
Varying degrees of immune response to antigens are seen both in terms of the intrinsic nature of the particular antigens and also in terms of the individual response of a subject to their presence. A given antigen may comprise a single immunostimulatory epitope or it may comprise a number of epitopes, each of which has its own potential level of immunostimulatory effect. Stimulatory activity of an antigen may also be increased by the use of a supplementary treatment called an adjuvant.
The series of events created by the presence of a particular antigen in a subject is typically described in reviews and textbooks on Immunology as leading to generation of a singular immune state. For example, in immunization a specific humoral and/or cellular response against the immunogen is induced. This “mono-static” view predicts mutually exclusive results of either a state of immune responsiveness or a state of immune suppression. In prior art, attempts at alteration of a pre-existing immune state are still of a unidirectional nature. These have been used either for the purpose of extending or boosting a particular immune response or leading to the reversal or suppression of the immune response. With reference to a particular immune target, either case is a change from one particular singular state to a different singular state. Thus, it would be predicted that treatments that lead to reduction or elimination of any aspect of immune reactivity towards a pathogen should result in allowance of further progression in either expression or growth of the pathogen by releasing the pathogen from immune control. This point has been discussed previously in a pending patent application, U.S. Ser. No. 08/808,1629 filed Feb. 28, 1997 which is incorporated by reference in its entirety, where it was suggested that drug treatments suitable for the pathogen would have to be used in conjunction with an immune therapy treatment. However, the drawback of a need for such dual therapeutic or pathogen management procedures was considered to be outweighed by benefits that would be provided by the reduction of immune responses that contribute to aspects of the disease state. Examples of such undesirable immune derived aspects are the inflammation and tissue destruction that are the hallmarks of chronic HBV and HCV infection. Thus, according to previous views a decrease in undesirable immune reactivity should also induce a decrease in other immune responses that may be beneficial for the continued health of the subject.